tbuckley/cabot-search huggingface dataset:
Perioperative chemotherapy with LP002, an anti-PD-L1 antibody, in patients with resectable gastric and gastroesophageal junction cancer: A prospective, open-label, phase Ib trial.
Authors: Jialin Tang, Jing Huang, Bo Zhang, Ling Qi, Xin Dao, Lin Wang, Yong Li, Yantao Tian
Journal: Journal of Clinical Oncology (2022)

4041 Background: Immune checkpoint inhibitors were effective, either alone or in combination with chemotherapy, in pts with metastatic gastric or gastroesophageal junction (GEJ) cancers, but their role for resectable disease remained unknown. We report the safety and pathological response of gastric/GEJ cancer pts receiving LP002, an anti-PD-L1 antibody, plus chemotherapy as perioperative treatment in a phase Ib trial. Methods: We enrolled pts with previously untreated, PD-L1 positive, resectable (cT2-4a, any N, M0) gastric/GEJ cancer. Eligible pts received three preoperative and six postoperative 2-week cycles of intravenous LP002 900mg on day 1, intravenous cisplatin 50 mg/m 2 on day 1, and 2000 mg/m 2 5-fluorouracil as 48-h infusion starting on day 1. The standard surgery was scheduled 4-6 weeks after completion of 3 cycles of preoperative treatment. The primary endpoint was safety. Secondary endpoints included proportion of pts with R0 resection and pathological complete response (pCR), disease-free survival, and overall survival. With pre- and post-treatment samples, we also characterized genomic changes in tumor tissue with next generation sequencing (NGS), and alterations in the tumor immune microenvironment (TIME) using multiplex immunofluorescence staining. Results: From September 2020 to July 2021, 30 pts were enrolled into this study. The median age was 64.5 years (range, 50-74). Most primary tumors were in the GEJ (N=28, 93.3%). 29 pts (96.7%) had adenocarcinoma, and 1 had small cell neuroendocrine tumor. The median follow-up duration was 7.9 months (range: 5.1-10.6) as of data cut-off (November 1, 2021). All pts completed the planned preoperative treatment, and 27 pts (90.0%) proceeded to surgery. Reasons for surgery not being performed were metastatic disease in 1 patient, and patient request in 2 cases. 24 pts had R0 resection, while 3 underwent R1 resection. 1 patient achieved pCR (TRG 1 per the Mandard’s tumor regression grading system) and 5 pts (18.5%) reached TRG 2-3. Treatment-related adverse events (TRAEs) were observed in 27 pts during perioperative treatment. Most of the TRAEs were of grade 1 to 2. The most common grade 3 toxicities were nausea (23.3%), neutrophil count decreased (16.7%) and anorexia (6.7%). 11 pts had immune-related adverse events, mostly grade 1 hyperthyroidism (45.5%). There were no grade 4-5 TRAEs. NGS analysis revealed that the mutation frequencies of the 733 genes in the sequencing panel decreased after preoperative treatment in pts with TRG 2-3. The analysis of TIME is undergoing. Conclusions: LP002 plus cisplatin and 5-fluorouracil was safe in pts with resectable gastric or GEJ cancer, and could be a new perioperative treatment option for PD-L1 positive disease. Pts are followed-up for survival outcomes. Clinical trial information: NCT04755543.
Metastasectomy in synovial sarcoma: A systematic review.
Authors: Bader Alshamsan, Megan Delisle, Denise Smith, Ying Wang, Amirrtha Srikanthan
Journal: Journal of Clinical Oncology (2022)

e23555 Background: Synovial sarcoma (SS) is a malignancy with high metastatic potential. The role of metastasectomy in SS is unclear, with limited data on prognostic factors and clinical outcomes. In this systematic review, we evaluate the survival outcomes post-metastasectomy for patients with SS. Methods: A systematic review was undertaken following PRISMA guidelines. English studies reporting survival outcomes among adults and children with SS undergoing metastasectomy were evaluated. Databases were searched from inception to May 31, 2021, and included Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. Two reviewers independently undertook literature evaluation and screening, data extraction and grading of studies. Risk of bias assessments utilized the Newcastle-Ottawa Quality Assessment Scale for Cohort Studies and the Joanna Briggs Institute Critical Appraisal Checklist for Case Series. Qualitative data was summarized in descriptive format, and survival outcome data were assessed for meta-analysis. Results: Thirteen retrospective studies, published between 1993 to 2017, were included, six were cohort studies, and seven were case series. A total of 598 patients with SS were included, of whom 462 had metastatic pulmonary disease, and 309 underwent metastasectomy. The median ages of the study cohorts ranged from 14 to 51 years. The median survival period after metastasectomy ranged from 21 to 80 months. The most common prognostic factors associated with survival included a disease-free interval (DFI) of greater than 12 months and complete resection of the metastases. Conclusions: The current literature has demonstrated that metastasectomy, particularly pulmonary, is a reasonable treatment option for appropriately selected patients with metastatic SS. Individuals with a DFI of greater than one year and who can safely undergo a complete resection appear the derive the greatest benefit. Registration: This protocol has been registered within the international prospective register of systematic reviews (PROSPERO) database (registration ID: CRD42019126906).
A tumor immune microenvironment-related lncRNA signature for the prognosis and immunotherapeutic sensitivity prediction in colorectal cancer.
Authors: Chuling Hu, Du Cai, Min-Er Zhong, Dejun Fan, Cheng-Hang Li, Min-Yi Lv, Ze-Ping Huang, Wei Wang, Xiaojian Wu, Feng Gao
Journal: Journal of Clinical Oncology (2022)

3543 Background: As important molecules in the CRC tumor microenvironment (TME), long non-coding RNAs (lncRNAs) regulate the functions of tumor infiltrating immune cells and sculpt the tumor immune microenvironment (TIME), resulting in difference in survival and response to immunotherapy among CRC patients. However, challenges remain in selecting TIME related lncRNAs (TIME-lncRNAs) of prognosis value and stratifying CRC patients for immunotherapy. Here, the aim of our study was to develop a CRC TIME-lncRNAs signature to provide survival and immunotherapy response predictions. Methods: Gene expression profiles and clinical information of CRC cases (n = 1807) were collected from 7 datasets and divided into training cohort (n = 519) and two testing cohorts (n = 595 and 693, respectively). Utilizing gene expression data of 97 immune cell lines and 61 CRC cell lines, differential expression analysis was used to identify TIME-lncRNAs. Univariate Cox regression and LASSO regression analysis were used to establish a TIME-lncRNAs signature to predict the prognosis of CRC patients. To further investigate the model, multivariate Cox regression, lncRNA-mRNA regulation analysis, gene enrichment analysis and immune infiltration analysis were carried out. The immunotherapy response predicting ability of the model was verified with an independent immunotherapy dataset. Results: Integrating the expression profiles of 10 TIME-lncRNAs, the model stratified CRC patients into low and high-score groups. Patients of the low score group had significantly prolonged survival in both training (hazard ratio (HR) = 2.63, 95% confidence interval (CI) = 1.9-3.63, P &lt; 0.001) and testing cohorts (testing cohort 1: HR = 1.6, 95% CI = 1.19-2.16, P = 0.002; testing cohort 2: HR = 1.64, 95% CI = 1.19-2.26, P = 0.002), while higher tumor purity and less pro-tumor immune cells infiltration were also observed in the low score group. Further investigation showed that both genes differentially expressed between different groups and mRNAs regulated by 10 lncRNAs of the signature were enriched in immune-related and immunotherapy-related pathways. Multivariate Cox regression indicated that the TIME-lncRNAs signature was an independent prognosis factor. Validated with external immunotherapy dataset, the signature provided distinct predictions for patients’ responses to PD-L1 inhibitor therapy, suggesting cases of high score group could benefit more from immunotherapy. Conclusions: Based on the expression of 10 lncRNAs in the TIME, the signature makes predictions for patients’ survival and immunotherapy responses, which could help in stratifying CRC patients for immunotherapy at the bedside.
Association of socioeconomic status with adherence to oral agents in patients with multiple myeloma.
Authors: Wilbur Rutter, Shivaani Prakash, William Cavers, Elisea Avalos-Reyes, Kjel Andrew Johnson, Leon Bernal-Mizrachi
Journal: Journal of Clinical Oncology (2022)

8023 Background: The introduction of novel oral immunomodulatory drugs has improved the overall survival rates of patients with multiple myeloma (MM). Poor adherence to oral therapies may lead to drug resistance, poor response to treatment and other downstream effects. It is unknown if socioeconomic status (SES) mediates adherence to oral MM agents. Methods: This is a retrospective review of newly diagnosed adult patients with MM with drug coverage through a large pharmacy benefit manager (PBM) who received oral MM agents between September 1, 2016 and September 1, 2020. Patients were excluded if they were not eligible for PBM benefits for the 6 months prior to or the 12 months after the index date and if they had a stem cell transplant based on a proxy signal. Adherence was defined as an annual medication possession ratio between 0.8 and 1.2. An SES composite index was developed using ZIP code level factors in a K-means clustering algorithm. Multivariable logistic regression for adherence was conducted using the SES-index and controlled for other patient-specific demographics. Results: In total, 6,602 patients were enrolled in the study, of which, 4,211 (64.5%) were defined as adherent. There were significant unadjusted differences in age (67.89 vs 64.06, p&lt;0.00001), ZIP code-based SES index (p=0.00049), census region (p&lt;0.00001) and insurance plan type (p&lt;0.00001). Results from multivariable logistic regression are shown in table. Patients residing in Very Low SES ZIP codes were significantly less likely to be adherent to oral MM agents compared to those residing in Very High SES locations. Odds of adherence increased as patient’s age increased. Increasing polypharmacy was negatively associated with oral MM agent adherence. Conclusions: Aside from patients residing in Very Low SES ZIP codes, ZIP code-based SES measures were not associated with worse adherence. Other mediating factors include younger age and number of co-prescribed medications. Further investigations of adherence to oral MM agents with clinically relevant outcomes are warranted. [Table: see text]
A phase II study of pemetrexed and pembrolizumab in recurrent and/or metastatic salivary gland malignancies.
Authors: Katharine Andress Rowe Price, Nathan R. Foster, Harry E. Fuentes Bayne, Casey Fazer, Panayiotis Savvides, Yujie Zhao, Patrick Walsh McGarrah, Anna C. Cooper, Ashish V. Chintakuntlawar
Journal: Journal of Clinical Oncology (2022)

TPS6111 Background: Treatment options for recurrent and/or metastatic (R/M) salivary gland cancer (SGC) are limited with response rates to standard cytotoxic chemotherapy (CT) low at 10-30%, and responses to single-agent immune checkpoint inhibition (ICI) &lt;10%. Current therapeutic agents used to treat R/M SGC have an unfavorable toxicity profile including cytotoxic CTs such as cisplatin and doxorubicin and the targeted therapy lenvatinib. Treatments with general applicability and acceptable side effect profile are urgently needed. Pemetrexed (PTX) is a multi-targeted anti-folate CT with an excellent safety and toxicity profile with promising responses reported in a case series of patients (pts) with R/M SGC (Viscuse P and Price K. Marked responses to pemetrexed chemotherapy for metastatic adenocarcinoma of the parotid gland: case series. Head Neck 2019;41(6):E99-103.). As the combination of PTX and pembrolizumab (PMB) showed enhanced responses and survival in pts with lung cancer, we hypothesize that PTX and PMB will have efficacy in pts with R/M SGC and that the combination will have improved anti-cancer activity compared with historical controls. Correlative studies on archived tissues include methylthioadenosine phosphorylase loss, PDL1 expression, and thymidylate synthase expression as potential biomarkers of response. Methods: MC200708 is a single institution (3-site), open-label, single arm phase II study of PTX and PMB in patients with R/M SGC. Pts will be treated in two cohorts: one for pts with adenoid cystic carcinoma (ACC) and the other for pts with all other types of SGC (non-ACC cohort). Eligible pts must be ≥18 years old, have a pathologically confirmed SGC that is not amenable to curative-intent therapy, ECOG 0-2, adequate organ function, and at least 1 measurable lesion by RECIST 1.1. Any number of lines of prior therapy is allowed; prior treatment with checkpoint inhibitors and/or PTX is allowed. Key exclusion criteria: serious medical co-morbidity or autoimmune disease, prior grade 3-4 adverse event (AE) or grade 2-4 lung AE with ICI, and uncontrolled brain metastases. Simon’s two-stage design will be used for each cohort separately given the expected difference in responses in pts with ACC and non-ACC. Primary endpoint is overall response rate. Secondary endpoints are progression free and overall survival and toxicity. All patients will receive the same treatment of PTX 500 mg/m2 IV + PMB 200 mg IV every 3 weeks until disease progression or treatment intolerance. Response assessments will occur every 3 cycles. Enrollment began July 2021 and 16 of the planned 45 patients (ACC cohort 9 of 20 pts, non-ACC 7 of 25) have been accrued. Clinical trial information: NCT04895735.
Efficacy and safety of second-line regorafenib after sorafenib or lenvatinib first line in patients with unresectable hepatocellular carcinoma: A real-world study.
Authors: Feng Xue, Jian Zhai, Jianwei Liu, Zhigang Fu, Yanfu Sun, Ruiliang Ge, Shilei Bai, Xiaowei Li, Kui Wang, Zengqiang Qu
Journal: Journal of Clinical Oncology (2022)

e16125 Background: To explore the safety, efficacy and long-term prognosis of patients with unresectable hepatocellular carcinoma (HCC) treated with regorafenib after failure of first-line treatment. Methods: This retrospective single center study included 50 unresectable HCC patients who received regorafenib as a second line treatment in our hospital. Based on the difference of first-line targeted drugs, the 50 patients were divided into sorafenib group (n = 22) and lenvatinib group (n = 28). The adverse events, efficacy and long-term prognosis of sorafenib or lenvatinib followed by regorafenib were analyzed. Results: The median age of the 50 patients was 54.5 years. The patients had the following clinical characteristics: ECOG score 0-1, HbsAg positive, cirrhosis, BCLC stage B/C in 95.5%, 95.5%, 90.9% and 90.9% of all patients respectively. The baseline clinical characteristics between the sorafenib and lenvatinib groups were not statistically different (all p &gt; 0.05), except for age and total bilirubin which were in favour of lenvatinib group. Regorafenib was administered oral 160 mg once daily during weeks 1–3 of each 4-week cycle. For 50 HCC patients, the incidence rate of adverse events after accepting regorafenib was 68%. The incidence rate of grade I/II and III/IV adverse events was 60% and 24%, respectively. According to the standards of RECIST 1.1 and mRSCIST, objective response rate (ORR) and disease control rate (DCR) after receiving regorafenib were 14.0%, 62.0% and 22.0%, 60.0%, respectively. There was no significant difference in incidence of all adverse events and grade III/IV adverse events, ORR and DCR between the two groups ( p &gt; 0.05). In terms of long-term prognosis, total overall survival (TOS) and regorafenib overall survival (ROS) in sorafenib group and lenvatinib group were 23.0 months (95% confidence interval [CI]: 15.1-30.9) vs. 29.7 months (95CI: 21.4-38.1), and 11.7 months (95CI: 7.1-16.3) vs. 15.9 months (95CI: 8.3-23.5). The difference was statistically significant ( p= 0.041 and P = 0.045). The regorafenib progression-free survival (RPFS) was 5.6 months (95CI: 1.9-9.2) vs. 8.0 months (95CI: 5.1-10.9) in sorafenib group and lenvatinib group, respectively. The difference was not statistically significant ( P = 0.380). Conclusions: The data suggest that regorafenib is an effective drug for second-line treatment of HCC, with an acceptable toxicity level, an ORR of 14%-22% and a DCR of 62%-60%. Both TOS and ROS in lenvatinib group are better than those in sorafenib group. The possible mechanisms was that EGFR activation limits the response of HCC cells to lenvatinib. For HCC patients whose first-line targeted drug is lenvatinib, it is safe and effective to accept regorafenib after the disease progresses.
The use of sentinel lymph node biopsy in patients undergoing mastectomy for DCIS.
Authors: Morgan K. Johnson, Chandler Scott Cortina, Mohammed Aldakkak, Amanda L. Kong
Journal: Journal of Clinical Oncology (2022)

e12572 Background: Current NCCN guidelines do not recommend sentinel node biopsy (SLNB) for the treatment of DCIS, except in the setting of a mastectomy. The extent of utilization of SLNB in patients undergoing mastectomy for DCIS and which factors are associated with a higher likelihood of SLNB use is unknown. The objective of this study is to evaluate the use of SLNB in patients undergoing mastectomy for DCIS and determine predictors of SLNB utilization. Methods: A retrospective cohort analysis was performed using the NCDB. Women diagnosed with DCIS who underwent a unilateral or bilateral mastectomy from 2012-2017 were included. Patient, tumor, and treatment variables were compared between patients who received a SLNB and those who did not. A multivariate logistic regression model was then used to identify factors predictive of SLNB utilization. Results: A total of 29,962 patients met inclusion criteria. Of these, 25,734 (85.9%) underwent SLNB and 4,228 (14.1%) had no surgical axillary staging. Most patients were age 50-69 (52.0%), non-Hispanic white (71.7%), and had private insurance (65.9%). In those who underwent SLNB, only 10 (&lt;0.01%) were found to have nodal involvement. On multivariate analysis, older patients were less likely to receive SLNB ( p&lt;0.05), while those with grade 2 and 3 DCIS were more likely to undergo SLNB (OR 1.4 and 2.2, respectively, p&lt;0.001) (Table). Patients who were treated from 2014-2017 were also more likely to undergo SLNB (OR 1.2, p&lt;0.01) as were patients treated in the Atlantic and West Central United States ( p&lt;0.05). Treatment at a comprehensive community program, academic/research program, or integrated network program were also more likely to undergo SLNB (OR 1.5, 2.1, 2.3 respectively, p&lt;0.001) compared to community programs. Conclusions: Patterns of SLNB utilization in DCIS varied in clinical practice. Given the low rate of nodal involvement in DCIS patients (&lt;0.01%), and with a 5-10% rate of upper extremity lymphedema after SLNB alone, it may be reasonable to omit SLNB in the setting of a mastectomy for DCIS.[Table: see text]
Long-term outcomes in EV-301: 24-month findings from the phase 3 trial of enfortumab vedotin versus chemotherapy in patients with previously treated advanced urothelial carcinoma.
Authors: Jonathan E. Rosenberg, Thomas Powles, Guru P. Sonpavde, Yohann Loriot, Ignacio Duran, Jae-Lyun Lee, Nobuaki Matsubara, Christof Vulsteke, Daniel E. Castellano, Ronac Mamtani, Chunzhang Wu, Maria Matsangou, Mary S. Campbell, Daniel P. Petrylak
Journal: Journal of Clinical Oncology (2022)

4516 Background: Enfortumab vedotin (EV), an antibody-drug conjugate directed against Nectin-4, demonstrated longer overall survival (OS) and progression-free survival (PFS) in the confirmatory phase 3, randomized, open-label EV-301 trial at the prespecified interim analysis. The longer-term clinical profile of EV is unknown. Data from 12 additional months of follow-up in EV-301 are presented. Methods: In EV-301 (NCT03474107), patients with locally advanced or metastatic urothelial carcinoma (la/mUC) who had received a prior platinum-containing chemotherapy and had disease progression during or after PD-1/L1 inhibitor treatment were randomized 1:1 to receive either EV 1.25 mg/kg on Days 1, 8, and 15 of each 28-day cycle or investigator-chosen standard chemotherapy with docetaxel, paclitaxel, or vinflunine. The primary endpoint was OS; secondary endpoints included investigator-assessed PFS per RECIST v1.1, as well as safety and tolerability. Efficacy and safety findings from July 30, 2021, approximately 1 year after the interim analysis (July 15, 2020), are reported. Results: Overall, 608 patients with la/mUC were randomly assigned to EV (n = 301) or chemotherapy (n = 307). As of July 30, 2021, 444 deaths had occurred (EV, n = 207; chemotherapy, n = 237). After a 23.75-month follow-up, median OS was significantly prolonged by 3.97 months with EV compared with chemotherapy (median OS: 12.91 vs 8.94 months, respectively; HR = 0.704 [95% CI: 0.581-0.852], 1-sided P= 0.00015). Additionally, the OS benefit of EV was retained in the majority of prespecified subgroups. PFS also was improved with EV (median 5.55 months) vs chemotherapy (median 3.71 months) (HR = 0.632 [95% CI: 0.525-0.762]; 1-sided P&lt; 0.00001). Rates of treatment-related adverse events (TRAEs; 93.9% vs 91.8%), including serious TRAEs (22.6% vs 23.4%), were comparable between the EV and chemotherapy groups. Rates of grade ≥3 TRAEs were ̃50% in both groups. Conclusions: EV continues to show significant and consistent survival advantage over standard chemotherapy in patients with treatment-experienced la/mUC. No new safety signals were identified. With robust clinical benefit and a tolerable safety profile, EV maintains its place as a standard of care for this aggressive disease. Clinical trial information: NCT03474107.